The present invention is generally in the area of compositions for lowering blood lipids, and specifically relates to compositions derived from shanzha fruit.
Hyperlipidemias, particularly hypercholesterolemia and the hyperlipoproteinemias, are among the most potent risk factors in the causation of atherosclerosis. Hyperlipoproteinemias are also implicated in the development of pancreatitis. A long-established theory suggests that the higher the circulating levels of low density lipoprotein, the more likely they are to gain entrance to the arterial wall and cause atherosclerosis. (M.S. Brown and J. L. Goldstein, "The Hyperlipoproteinemias and Other Disorders of Lipid Metabolism," in Harrison's Principles of Internal Medicine 1650-1661, (E. Braunwald et al. 1987)).
Lipoproteins, including intermediate density lipoprotein (IDL) and low density lipoprotein (LDL), are the major carriers for triglycerides and cholesterol, in the form of cholesteryl esters, in the plasma. The core of an IDL or LDL particle is cholesterol rich. About three-fourths of the total cholesterol in normal human plasma is contained in LDL particles. In the liver, LDL is taken up from the blood through binding to LDL receptors on hepatocytes. In humans, 70 to 80 per cent of LDL is removed from the plasma each day by the LDL receptor pathway in hepatocytes.
Some of the cholesterol from LDL particles is used by hepatocytes in the synthesis of bile acids, which are excreted along with some free cholesterol through the biliary system into the intestine, and some is used in the cell for synthesis of cellular membranous organelles or distributed to other tissues for use in organelle and steroid hormone synthesis. If uptake is blocked at the receptor level, cholesterol accumulates in the blood and can contribute to atherosclerosis.
Cells needing cholesterol for membrane synthesis make LDL receptors and insert them into the cell membrane, where they associate with coated pits. When LDL receptors bind LDL, the coated pits pinch off into the cytoplasm, form coated vesicles, and thereby internalize LDL into the cell. LDL receptors are subsequently recycled to the cell membrane, and the cholesterol is used in membrane synthesis. If too much cholesterol accumulates in a cell, the cell's own synthesis of cholesterol and LDL receptor protein is shut down. Then less cholesterol is taken up by the cell.
In hypercholesterolemia, the increase in the blood cholesterol level is associated mainly with a rise in LDL concentrations. However, the specific causes of hypercholesterolemia are complicated, varied, and largely, unknown. At least one kind of hypercholesterolemia is caused by a mutation in the gene for the LDL receptor. Both heterozygotes and homozygotes for the defect manifest a significant elevation in the concentration of total plasma cholesterol, which is attributable to an elevation in the level of serum LDL.
Reduction of hypercholesterolemia results in a delayed onset of atherosclerosis and a decrease in progression of atherosclerosis, thus reducing the risk of coronary heart disease in humans and other primates. Specifically, there is evidence in animals, most notably primates, that relatively complicated plaques induced by hyperlipidemia will regress, and that further progression of atherosclerosis will cease when hyperlipidemia is removed. Therefore, efforts to prevent atherogenesis, to interrupt progression, and perhaps to promote regression of existing lesions by risk factor reduction are warranted. E. L. Bierman, "Disorders of the Vascular System: Atherosclerosis and Other Forms of Arteriosclerosis," in Harrison's Principles of Internal Medicine 1014-1024, (E. Braunwald et al. 1987).
Some forms of hyperlipidemia, including hypercholesterolemia, are potentially partially reversible with current techniques of preventive management. However, none of the current techniques is completely successful and many are associated with unwanted side effects and complications. Dietary therapy is usually recommended for patients with hypercholesterolemia but is not always effective. Methods that result in an increased production of LDL receptors, thus allowing the liver to take up more LDL from blood, have also been proposed. For example, bile acid binding resins, such as cholestyramine, may be used to trap the bile acids excreted by the liver. When bile acids are depleted, the liver responds by converting additional cholesterol into bile acids. To step up the synthesis of bile acids, an enhanced production of LDL receptors by the liver occurs, which in turn lowers the plasma level of LDL. One complication of this approach to treating high serum cholesterol by reduction of bile acids is that the liver may also respond to bile acid depletion by enhancing cholesterol synthesis. Bile acid binding resins may also cause gastrointestinal bloating, cramps, and constipation.
Methods for treating disease states associated with high blood levels of lipids by increasing the number of LDL receptors in hepatocytes by a class of drugs that exhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA reductase), an enzyme involved in cholesterol synthesis, have also been proposed. However, long term administration of HMGCoA reductase inhibitor may lead to a suppression of cholesterol synthesis that in turn may affect the availability of precursor for essential steroid hormones such as mineralocorticoids, glucocorticoids, and the sex hormones. Further, some patients using HMGCoA reductase inhibitor have developed cataracts prematurely. Accordingly, what is needed are other effective methods and compositions for use in lowering blood lipid levels and in treating disease states associated with high levels of blood lipids.
It is therefore an object of the present invention to provide compositions and methods of use to treat high blood lipid or lipoprotein levels and disease states related to each of these.
It is a further object of the present invention to provide compositions and methods of use to treat hypercholesterolemia and related disease states, such as atherosclerosis.